title: New orally effective 3-(2-nitro)phenylpropanamide analgesic derivatives: synthesis and antinociceptive evaluation.
abstract: A series of substituted 6-nitrophenylpropanamide derivatives (1-20) were synthesized using either the TDAE strategy or classical organic reactions. All these compounds were characterized by fusion point, (1)H NMR, (13)C NMR, elemental analysis or mass spectrometry data. Because of their structural analogy with recently published compounds possessing antinociceptive properties, our derivatives were screened for peripheral analgesic activities on acetic acid-induced writhing in mice. Compound 13 showed the best result at 100 μmol/kg ip (50% inhibition vs 59% for aspirin). This antinociceptive activity was maintained after oral administration (40% inhibition vs 31.6% for aspirin). Both hot-plate and actimetry-based tests were non-significant suggesting the analgesic activity of 13 linked to a peripheral mechanism.
authors.affiliation: Aix-Marseille Univ, UMR CNRS 7273, Institut de Chimie Radicalaire, Equipe Pharmaco-Chimie Radicalaire (LPCR), Faculté de Pharmacie, 27 Boulevard Jean Moulin, CS 30064, 13385 Marseille Cedex 5, France. Electronic address: marc.since@unicaen.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Since
authors.forename: Thomas
authors.initials: T
authors.lastname: Freret
authors.forename: Gerald
authors.initials: G
authors.lastname: Nee
authors.forename: Thierry
authors.initials: T
authors.lastname: Terme
authors.forename: Patrice
authors.initials: P
authors.lastname: Vanelle
authors.forename: Michel
authors.initials: M
authors.lastname: Boulouard
mesh_terms: D019342:Acetic Acid; D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D052117:Benzodioxoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D010879:Piperazines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C000589301:1-(4-(4-methoxyphenyl)piperazin-1-yl)-3-(6-nitrobenzo(d)(1,3)dioxol-5-yl)propan-1-one; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052117:Benzodioxoles; D010879:Piperazines; D019342:Acetic Acid
keywords: 6-Nitrophenylpropanamide; Analgesic; Hot-plate test; Peripheral antinociceptive activity; TDAE; Writhing test